Chloroquinoxaline sulfonamide is a halogenated sulfonamide with preclinical activity in the human tumor cell clonogenic assay. Clinical trials of monthly or weekly bolus therapy have been limited by severe hypoglycemia (HG) probably related to peak CQS concentrations. We therefore designed a Phase I trial using an intravenous (iv) loading dose followed by a 7-day continuous iv infusion (loading dose (mg/m2)/daily infusion dose (mg/m2/day)) each month. Thirteen patients (pts) have now received 25 courses at dose levels of 400/100, 800/200, 1200/300, and 1600/400. Tumor types include lung (5 pts), head and neck (4 pts), breast (1 pt), esophagus (1 pt), colon (1 pt), and pancreas (1 pt). Nine pts had received prior radiotherapy and 13 prior chemotherapy. Estimates for derived pharmacokinetic parameters were generally consistent with those from CQS bolus studies. Representative ranges for terminal elimination half-life, Vdss and CI were 35-94 hr, 6-10 1/m2 and 70-140 ml/hr/m2, respectively. Mild dose-related HG was seen on Day 1 of each infusion but was not dose-limiting and resolved within 12 hours despite continued CQS infusion. HG was acccompanied by hyperinsulinemia which also resolved within 12 hours. Dose-limiting toxicity at 1600/400 consisted of myclosuppression (Grade 4 in 2/6 pts and Grade 3 in 2/6 pts). Mild mucositis, alopecia and nausea/vomiting were also seen at 1600/400. One pt with head and neck cancer had a minor response lasting 3 months. Additional patients were being treated to confirm 1200/300 as the recommended dose for further studies.